Applications of enzymes in synthetic carbohydrate chemistry

Abstract

By photosynthesis 200 billion tons of glucose are formed per annum most of which remains in the sugar state. Thus, the well-known properties of saccharides as the basis for structural materials and energy stores is well established. Increasingly, focus is being addressed to their functions as recognition molecule. Therefore, carbohydrate chemistry became en vogue again as documented by classical syntheses of complex hetero-oligosaccharides employing protecting and activating group chemistry. In recent years enzymatic methods for acylation and deacylation in saccharide chemistry came into use. Novel saccharides could be approached following aldolase-catalyzed de novo syntheses. The very complex task of stereospecific glycosylation was addressed by use of enzymes. With glycohydrolases via transglycosylation as well as with glycosyltransferases including cofactor regenerating circles advances were made. Modified acceptor and also donor substrates allowed access to oligosaccharides in preparative quantities. This paper will discuss these modem developments and will focus on some selected examples from others' and our own laboratory.

An original chemoenzymatic route for the synthesis of β-d-galactofuranosides using an α-l-arabinofuranosidase

“…Increasingly, to simplify some or all of the synthetic steps for the production of oligosaccharides, enzymatic or chemoenzymatic strategies are being adopted. 22,23 Generally, by default, O-glycosidases and glycosyl transferases catalyse the modification of glycosidic bonds in a stereospecific manner and, in addition, are often regiospecific. Therefore, the use of such enzymes for synthesis can eliminate lengthy protection/deprotection procedures and drastically reduce both the time required and the use of organic solvents and other undesirable chemicals.…”

Fermentation Process Development of Carbohydrate-Based Therapeutics

“…In the chemical route, regioselectivity is the prominent issue in carbohydrate chemistry and the undesired reactions of the hydroxyl groups of the sugars should be properly protected during reaction and deprotected afterwards as examplied by a classical disaccharide synthesis in Fig. 2 (8). In spite of the impressive development of novel and efficient methods for the synthesis of complex carbohydrates, these expensive protection and deprotection sequences might still limit their industrial applications (8,10,28).…”

“…2 (8). In spite of the impressive development of novel and efficient methods for the synthesis of complex carbohydrates, these expensive protection and deprotection sequences might still limit their industrial applications (8,10,28). This might be avoided by using another route: enzymatic synthesis.…”

“…Likewise, many reviews focusing on utilizing enzymes in carbohydrate synthesis are emerging (8)(9)(10). Since most of the complex bioactive carbohydrates are produced in nature by enzymes, specific enzymes capable of regioselective transfer and high glycosylation yields have been characterized and used for synthesizing carbohydrate-based therapeutics.…”

1998 Hoffmann La Roche Award Lecture Understanding and exploiting glycosidases

“…While classical organic synthetic approaches are able to yield almost any oligosaccharide needed, the quantities of compound available through such routes are typically very limited. Enzymatic synthesis provides an alternative approach, and indeed glycosyl transferases, Nature's own biosynthetic catalysts, are finding increasing application as they become available in greater numbers (35)(36)(37)(38). However, the cost of the nucleotide diphosphosugars is still prohibitive.…”